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Background For a better understanding of the factors underlying the Post-Acute COVID Syndrome, we studied the relationship between symptoms and functional alterations in COVID-19 patients 10 months after hospitalization. Methods One-hundred-one patients hospitalized between March 1st and June 30th 2020 participated in a follow-up visit for an assessment of clinical history, comorbidities, lung function, physical capacity and symptoms, including the SGRQ for health-related quality of life, PHQ-9-D for depression, and SOMS-2 J for somatoform disorders. Data were analyzed by univariate comparisons and multiple logistic regression analyses. Results Median age was 60 years, 42% were female, 76% had at least one comorbidity, the median length of the hospital stay was 8 days, 19% had been on the ICU. The most prevalent symptoms included shortness of breath (49%), fatigue (49%) and cognitive impairment (39%). Signs of major depression (PHQ-9-D ≥ 10) occurred in 28%/2% (p

Chronic kidney disease (CKD) represents a global public health problem with high disease related morbidity and mortality. Since CKD etiology is heterogeneous, early recognition of patients at risk for progressive kidney injury is important. Here, we evaluated the tubular epithelial derived glycoprotein dickkopf-3 (DKK3) as a urinary marker for the identification of progressive kidney injury in a non-CKD cohort of patients with chronic obstructive pulmonary disease (COPD) and in an experimental model. In COSYCONET, a prospective multicenter trial comprising 2,314 patients with stable COPD (follow-up 37.1 months), baseline urinary DKK3, proteinuria and estimated glomerular filtration rate (eGFR) were tested for their association with the risk of declining eGFR and the COPD marker, forced expiratory volume in one second. Baseline urinary DKK3 but not proteinuria or eGFR identified patients with a significantly higher risk for over a 10% (odds ratio: 1.54, 95% confidence interval: 1.13-2.08) and over a 20% (2.59: 1.28-5.25) decline of eGFR during follow-up. In particular, DKK3 was associated with a significantly higher risk for declining eGFR in patients with eGFR over 90 ml/min/1.73m2 and proteinuria under 30 mg/g. DKK3 was also associated with declining COPD marker (2.90: 1.70-4.68). The impact of DKK3 was further explored in wild-type and Dkk3-/- mice subjected to cigarette smoke-induced lung injury combined with a CKD model. In this model, genetic abrogation of DKK3 resulted in reduced pulmonary inflammation and preserved kidney function. Thus, our data highlight urinary DKK3 as a possible marker for early identification of patients with silent progressive CKD and for adverse outcomes in patients with COPD.

Fractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and could replace bronchial provocation (BP). To date, cut-off values have been derived by post hoc analysis only. The aim was to validate the diagnostic accuracy for predefined FeNO cut-off values and the predictive value for responsiveness to inhaled corticosteroids (ICS).We conducted a prospective, diagnostic, multicentre study with patients attending three private practices of pneumologists in Upper Bavaria, Germany, from July 3, 2020 to Jan 21, 2022. Index test was FENO measurement. Reference standard was Tiffeneau ratio (FEV308 patients with complete follow-up were recruited, 186 (60·4%) were female, average age was 44·7 years, 161 (52·3%) had asthma. Regarding diagnostic accuracy, the area under the curve (AUC) was 0·718 (95% CI 0·661-0·775;FeNO measurement allows a valid ruling-in of an asthma diagnosis, whereas ruling-out of asthma is not possible. Enhanced probability of ICS responsiveness is also given with increased FeNO values.Circassia Germany gave 25% discount on the purchase of three NIOX VERO devices.

OBJECTIVES: The objective of the study is to determine the impact of changing reference standards (RS), namely spirometry vs. whole-body plethysmography (WBP), on estimation of the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) and clinical signs and symptoms (CSS) as index tests regarding asthma diagnosis. STUDY DESIGN AND SETTING: This was a diagnostic study conducted in 393 patients attending a private practice of pneumologists with complaints suspicious of asthma. First, the index tests were compared with the diagnostic results of spirometry in terms of forced expiratory volume in the first second (FEV1) responsiveness. Second, the index tests were compared with the results of WBP in terms of specific airway resistance and FEV1 responsiveness. Areas under the curve (AUC) were compared with a generalized estimating equation approach based on binary logistic regression. RESULTS: FeNO values and CSS 'wheezing' and 'allergic rhinitis' showed higher specificities (P

Background Regarding the multiple health effects of e-cigarettes, there are insufficient data on potential effects on bronchial reactivity (BHR). In the present study, we assessed the impact of a switch from conventional to e-cigarettes on BHR under realistic conditions over a period of 3 months. Methods Sixty subjects who declared to reduce or stop their tobacco consumption by inhalation of nicotine-containing liquids via e-cigarette, and 20 volunteers participating in a stop-smoking program were included. Data was analysed using parametric and non-parametric statistical procedures. Spirometry, determinations of exhaled carbon monoxide (eCO) and nitric oxide (FeNO), provocation testing with mannitol as an indirect bronchial stimulus, and cotinine measurements were used to investigate BHR and nicotine abstinence. Results BHR to mannitol significantly decreased in the group using e-cigarettes and nicotine-containing liquids over a period of three months in this real-life setting. Participants reduced their tobacco consumption to about 25% or lower, confirmed by a reduction in eCO. Changes in lung function and FeNO were small and not statistically significant, and changes in the stop-smoking group were similar to those in the e-cigarette group. Conclusion The reduction in BHR that can be expected after a reduction of cigarette consumption was not abolished by the concomitant use of e-cigarettes. Whether the decrease in BHR observed after 3 months is maintained when using e-cigarettes over longer time periods or has an individual prognostic value, must be clarified in long-term studies.

Background: Reliable up-to-date estimates regarding the economic impact of chronic obstructive pulmonary disease (COPD) are lacking. This study investigates COPD excess healthcare utilization, work absenteeism, and resulting costs within the German COPD cohort COSYCONET. Methods: Data from 2139 COPD patients in GOLD grade 1-4 from COSYCONET were compared with 1537 lung-healthy control subjects from the population-based KORA platform. Multiple generalized linear models analyzed the association of COPD grades with healthcare utilization, work absence, and costs from a societal perspective while adjusting for sex, age, education, smoking status, body mass index (BMI), and several comorbidities. Results: COPD was significantly associated with excess healthcare utilization, work absence, and premature retirement. Adjusted annual excess cost of COPD in 2012 for GOLD grade 1-4 amounted to €2595 [1770-3678], €3475 [2966-4102], €5955 [5191-6843], and €8924 [7190-10,853] for direct costs, and €8621 [4104-13,857], €9871 [7692-12,777], €16,550 [13,743-20,457], and €27,658 [22,275-35,777] for indirect costs respectively. Comorbidities contributed to the primary effect of COPD on direct costs only. An additional history of cancer or stroke had the largest effect on direct costs, but the effects were smaller than those of COPD grade 3/4. Conclusions: COPD is associated with substantially higher costs than previously reported.

Background: While exposure to ambient particulate matter (PM) and nitrogen dioxide (NO2) is thought to be associated with diseases via inflammatory response, the association between exposure to ozone, an oxidative pollutant, and inflammation has been less investigated.Aim: We analyzed associations between short-term exposure to ozone and three inflammatory biomarkers among children and adolescents.Methods: These cross-sectional analyses were based on two follow-ups of the GINIplus and LISA German birth cohorts. We included 1330 10-year-old and 1591 15-year-old participants. Fractional exhaled nitric oxide (FeNO) and high-sensitivity C-reactive protein (hs-CRP) were available for both age groups while interleukin (IL)-6 was measured at 10 years only. Maximum 8-h averages of ozone and daily average concentrations of NO2 and PM with an aerodynamic diameter = 120 mu g/m(3)) tended to be associated with elevated levels for both 10- and 15-year-old participants.Conclusions: Our study demonstrates significant associations between short-term ozone exposure and FeNO at 15 years of age and J-shaped relationship between ozone and hs-CRP. The finding indicates that high ozone exposure may favor inflammatory responses in adolescents, especially regarding airway inflammation.

Despite the recent popularity of e-cigarettes, to date only limited data is available on their safety for both users and secondhand smokers. The present study reports a comprehensive inner and outer exposure assessment of e-cigarette emissions in terms of particulate matter (PM), particle number concentrations (PNC), volatile organic compounds (VOC), polycyclic aromatic hydrocarbons (PAH), carbonyls, and metals. In six vaping sessions nine volunteers consumed e-cigarettes with and without nicotine in a thoroughly ventilated room for two hours. We analyzed the levels of e-cigarette pollutants in indoor air and monitored effects on FeNO release and urinary metabolite profile of the subjects. For comparison, the components of the e-cigarette solutions (liquids) were additionally analyzed. During the vaping sessions substantial amounts of 1,2-propanediol, glycerine and nicotine were found in the gas-phase, as well as high concentrations of PM2.5 (mean 197 μg/m(3)). The concentration of putative carcinogenic PAH in indoor air increased by 20% to 147 ng/m(3), and aluminum showed a 2.4-fold increase. PNC ranged from 48,620 to 88,386 particles/cm(3) (median), with peaks at diameters 24-36 nm. FeNO increased in 7 of 9 individuals. The nicotine content of the liquids varied and was 1.2-fold higher than claimed by the manufacturer. Our data confirm that e-cigarettes are not emission-free and their pollutants could be of health concern for users and secondhand smokers. In particular, ultrafine particles formed from supersaturated 1,2-propanediol vapor can be deposited in the lung, and aerosolized nicotine seems capable of increasing the release of the inflammatory signaling molecule NO upon inhalation. In view of consumer safety, e-cigarettes and nicotine liquids should be officially regulated and labeled with appropriate warnings of potential health effects, particularly of toxicity risk in children.

SummaryBackgroundPulmonary hypertension (PH) is considered a clinically important feature of Obesity-Hypoventilation Syndrome (OHS). We aimed to determine prevalence, characteristics and severity of PH including associations with clinical outcomes after established non-invasive positive pressure ventilation (NPPV).MethodsIn a prospective cross-sectional study, clinically stable OHS-patients (NPPV duration ≥ 3 months) were consecutively assessed using echocardiography, serum markers and right-heart catheterization (RHC). NPPV use was quantified via ventilator counters. Blood gases, lung function, Epworth-Sleepiness Scale (ESS), sleep-quality, WHO-functional class (WHO-FC), 6-min walk distance, and health-related quality of life (HRQL) via Severe Respiratory Insufficiency (SRI) questionnaire were assessed.ResultsOf 177 patients considered, 64 fulfilled inclusion criteria. Among these, 21 patients (10 female/11 male; BMI 45 [40; 53] kg/m2, PaCO2 39.6 [37.8; 45.5] mmHg (median [quartiles])) gave consent for RHC. Four patients (19%) had normal mean pulmonary artery pressure (mPAP

Physical Activity (PA) plays an important role in the health and quality of life of cystic fibrosis (CF) patients, but little is known about their PA in daily living. With the use of accelerometers it is now possible to monitor activity profiles in detail. The goals of this study are to assess feasibility and acceptance of a longer-term use of accelerometers in daily living in CF patients, study the possibility of detecting changes in PA in relation to the patients' clinical state and compare the findings between a CF and an age-matched healthy control group. We asked 15 CF patients to wear two accelerometers for 21 days and fill in a diary. Ten of them (age 21 to 40, mean 29.5 years) participated and delivered data that could be evaluated. We also recruited 10 age-matched control subjects. Data was processed for calculating usage time and features extracted to construct models of activity. The younger patients, particularly females, were concerned with fashion and style and considered wearing the sensors a challenge. Overall, the compliance of patients with CF seemed to be lower than reported for elder subjects in the literature. Time-series analysis of the data indicated characteristic patterns of PA over time, provided that data pre-processing and noise-filtering had been optimized. Further studies have to assess whether the continuous recording of PA yields additional clinical information in CF and in particular, whether it is possible to detect or even predict exacerbations in patients with CF or other diseases.

Summary Aim While it is known that severe COPD has substantial economic consequences, evidence on resource use and costs in mild disease is scarce. The objective of this study was to investigate excess costs of early stages of COPD. Methods Using data from two population-based studies in Southern Germany, current GOLD criteria were applied to pre-bronchodilator spirometry for COPD diagnosis and staging in 2255 participants aged 41 to 89. Utilization of physician visits, hospital stays and medication was compared between participants with COPD stage I, stage II+ (II or higher) and controls. Costs per year were calculated by applying national unit costs. In controlling for confounders, two-part generalized regression analyses were used to account for the skewed distribution of costs and the high proportion of subjects without costs. Results Utilization in all categories was significantly higher in COPD patients than in controls. After adjusting for confounders, these differences remained present in physician visits and medication, but not in hospital days. Adjusted annual costs did not differ between stage I (€ 1830) and controls (€ 1822), but increased by about 54% to € 2812 in stage II+. Conclusion The finding that utilization and costs are considerably higher in moderate but not in mild COPD highlights the economic importance of prevention and of interventions aiming at early diagnosis and delayed disease progression.

Summary Background Exacerbations of chronic obstructive pulmonary disease (COPD) significantly contribute to COPD-related morbidity. Diagnosis of COPD exacerbations may be improved by analyzing biomarkers such as alpha-1 antitrypsin (AAT). AAT is an acute-phase protein and inhibitor of neutrophil elastase. Deficiency of AAT may result in early-onset respiratory symptoms. Measurement of exhaled breath condensate (EBC) is a noninvasive method to investigate biomarkers present in the epithelial lining fluid, such as AAT. Objective To investigate whether AAT can be detected and quantified in EBC and to compare AAT levels in the EBC of healthy controls, patients with COPD, and during exacerbations of COPD. Methods EBC from 10 healthy controls, 17 subjects with COPD, and 18 subjects with exacerbations of COPD was collected with the RTube™ device. AAT from EBC and serum were quantified by ELISA. Results AAT in EBC was detectable in every individual. Patients with exacerbations of COPD had significantly increased AAT values (mean, 514.33pg/mL, [SD 279.41 ]) compared with healthy controls (mean, 251.32pg/mL, [SD 44.71]) and stable COPD patients (mean, 242.01pg/mL [SD 65.74]) ( P =0.0003; P =0.00003). EBC AAT showed only a correlation trend with serum AAT ( r =0.3, P =0.054). Conclusions AAT in EBC was detectable and quantifiable. AAT measured in EBC was significantly increased during exacerbations of COPD and can potentially be used as a biomarker in exacerbations.

Summary Background The evaluation of exhaled breath profiles by electronic nose (eNose) is considered as a promising non-invasive diagnostic tool, and the discrimination of breathprints between patients with COPD and asthma has been reported. The aim of this study was to assess, whether exhaled breath profile analysis can detect the inflammatory airway response induced by ozone inhalation. Methods In a randomized double-blind, cross-over study 14 healthy ozone-responsive subjects were exposed to 250ppb ozone and filtered room air for 3h with intermittent exercise. Blood biomarkers, exhaled NO, exhaled CO, and breathprints (Cyranose 320 ® ) were assessed prior and at 3 time points up to 24h post exposure. Induced sputum was collected at baseline and 3h post exposure. Multivariate analysis of eNose data was performed using transformed and normalized datasets. Results Significantly increased numbers of sputum and blood neutrophils were observed after ozone, whereas the eNose signals showed no differences between exposures and no correlation with neutrophilic airway inflammation. However, independent of ozone exposure, sensor data correlated with serum SP-D levels and to a smaller extent with blood neutrophil numbers. Conclusions Exhaled breath profiles as measured by the Cyranose 320 ® did not reflect airway responses to ozone. This suggests that exhaled volatiles did not change with ozone challenges or that the changes were below the detection limits. Conversely, the correlation of eNose signals with blood neutrophils and serum SP-D, i.e. markers of systemic inflammation and lung permeability, suggested that the Cyranose 320 ® can detect volatile organic compounds of systemic origin.

Summary Body plethysmography allows to assess functional residual capacity ( FRC pleth ) and specific airway resistance ( sRaw ) as primary measures. In combination with deep expirations and inspirations, total lung capacity (TLC) and residual volume (RV) can be determined. Airway resistance ( Raw ) is calculated as the ratio of sRaw to FRC pleth . Raw is a measure of airway obstruction and indicates the alveolar pressure needed to establish a flow rate of 1 L s −1 . In contrast, sRaw can be interpreted as the work to be performed by volume displacement to establish this flow rate. These measures represent different functional aspects and should both be considered. The measurement relies on the fact that generation of airflow needs generation of pressure. Pressure generation means that a mass of air is compressed or decompressed relative to its equilibrium volume. This difference is called "shift volume". As the body box is sealed and has rigid walls, its free volume experiences the same, mirror image-like shift volume as the lung. This shift volume can be measured via the variation of box pressure. The relationship between shift volume and alveolar pressure is assessed in a shutter maneuver, by identifying mouth and alveolar pressure under zero-flow conditions. These variables are combined to obtain FRC pleth , sRaw and Raw . This presentation aims at providing the reader with a thorough and precise but non-technical understanding of the working principle of body plethysmography. It also aims at showing that this method yields significant additional information compared to spirometry and even bears a potential for further development.

SummaryForced inspiratory measures have been described to reflect the reduction in dyspnoea upon bronchodilation in severe COPD. Based on this we evaluated the applicability and usefulness of a portable device for the assessment of forced inspiration. In 37 patients with COPD (GOLD II/II/IV n = 16/15/6, mean ± SD FEV1 46.2 ± 15.4%pred) lung function was recorded prior to inhalation of 24 μg formoterol and 30 min later. Assessments comprised spirometry including forced inspiration, body plethysmography, maximum inspiratory flow (InCheck, Clement Clarke), and changes in dyspnoea via visual analogue scale (VAS). The sequence was repeated on a second day to assess reproducibility. Bronchodilation by formoterol was detectable in all functional indices (p

In patients with chronic respiratory diseases body mass index (BMI) is a predictor of long-term survival, whereas the prognostic value of body composition, especially fat-free mass index (FFMI), is unknown.In a prospectively collected cohort of 131 patients (50 females, 81 males; 71% chronic obstructive pulmonary disease, 29% severe restrictive disorders) undergoing home mechanical ventilation (HMV) due to chronic hypercapnic respiratory failure (CHRF), the prognostic value of nutritional composition assessed by bioelectrical impedance analysis was evaluated during a 4-year follow-up and compared to that of BMI, anthropometrics, and functional parameters.After follow-up, 53 patients (40.5%) had died. Regarding all-cause mortality cumulative survival percentages after 1, 2 and 3 years were 89.3, 76.3 and 67.9%, respectively. In univariate analyses, FFMI, BMI, sex, age, leukocyte number, FEV1 and 6-min walking distance were associated with survival (p0.05). Multivariate analyses using the most significant percentiles identified by univariate analysis revealed FFMI (25th percentile; hazard ratio 0.338 [95% confidence interval: 0.189-0.605]), sex, leukocyte number (50th percentile) and FEV1 (50th percentile) as independent predictors of mortality.In patients with CHRF and HMV, body composition in terms of FFMI was an independent predictor of long-term survival. FFMI was superior to BMI and seems informative in the multidimensional assessment of these patients.

The smoke of waterpipe contains numerous substances of health concern, but people mistakenly believe that this smoking method is less harmful and addictive than cigarettes. An experiment was performed in a 57 m3 room on two dates with no smoking on the first date and waterpipe smoking for 4 h on the second date. We measured volatile organic compounds (VOC), polycyclic aromatic hydrocarbons (PAH), metals, carbon monoxide (CO), nitrogen oxides (e.g. NO), as well as particle mass (PM), particle number concentration (PNC) and particle surface area in indoor air. High concentrations were observed for the target analytes during the 4-h smoking event. The median (90th percentile) values of PM2.5, PNC, CO and NO were 393 (737 μg/m3), 289,000 (550,000 particles/cm3), 51 (65 ppm) and 0.11 (0.13 ppm), respectively. The particle size distribution has a maximum of particles relating to a diameter of 17 nm. The seven carcinogenic PAH were found to be a factor 2.6 higher during the smoking session compared to the control day. In conclusion, the observed indoor air contamination of different harmful substances during a WP session is high, and exposure may pose a health risk for smokers but in particular for non-smokers who are exposed to ETS.

Summary Methacholine testing is an important diagnostic tool for asthma. Newly available dosimeter and software technology allows for simplification of the test. This study aimed to evaluate a single-concentration dosimeter protocol for methacholine testing by comparison with a multi-concentration dosimeter protocol similar to that recommended by the American Thoracic Society (ATS) (standard protocol). Fifty young subjects with high pretest probability for bronchial hyperresponsiveness underwent two challenges in randomized order within one week. The novel protocol used a Medic-Aid Sidestream nebulizer and a fixed methacholine concentration of 16mg/mL. Number and duration of nebulizations were matched to the last four doses of the standard protocol, and results were expressed cumulatively. The rank correlation between log slopes ( n =50) was 0.86; that between log provocative doses ( n =18), which differed at low values, was 0.58. When requiring a 20% fall in FEV 1 at any methacholine dose, 18 subjects were hyperresponsive and 28 normoresponsive in both tests (46/50 concordant). One subject was positive only with the standard, and 3 only with the novel protocol (Cohen's kappa 83%). The novel protocol for methacholine testing yielded qualitative results similar to those of the ATS multi-concentration protocol, although there were quantitative differences at low doses. However, its design and handling may offer advantages for clinical practice.

Smoking is known to be linked to skin ageing and there is evidence for premature senescence of parenchymal lung fibroblasts in emphysema. To reveal whether the emphysema-related changes in cellular phenotype extend beyond the lung, we compared the proliferation characteristics of lung and skin fibroblasts between patients with and without emphysema. Parenchymal lung fibroblasts and skin fibroblasts from the upper torso (thus limiting sun exposure bias) were obtained from patients without, or with mild, or with moderate to severe emphysema undergoing lung surgery. We analysed proliferation rate, population doublings (PD), staining for senescence-associated beta-galactosidase (beta-gal) and gene expression of IGFBP-3 and IGFBP-rP1. Population doubling time of lung fibroblasts differed between control, mild, and moderate to severe emphysema (median (IQR) 29.7(10.0), 33.4(6.1), 44.4(21.2) h; p=0.012) and staining for beta-gal was elevated in moderate to severe emphysema. Compared to control subjects, skin fibroblasts from patients with emphysema did not differ with respect to proliferation rate, PD and beta-gal staining, and showed a lower abundance of mRNA for IGFBP-3 and -rP1 (p

Background The combined measurement of diffusing capacity of the lung for nitric oxide (Dlno) and diffusing capacity of the lung for carbon monoxide (Dlco) is a simple, noninvasive tool, but methodologic factors might influence results and reproducibility. We thus quantified the influence of breath-hold time on Dlco and Dlno in subjects with or without airway disease. Methods Simultaneous single-breath measurements of Dlco and Dlno were performed in 10 patients with cystic fibrosis (CF) [mean ± SD age, 33 ± 9 years; FEV 1 , 69 ± 28% of predicted] and 10 healthy subjects (age, 31 ± 9 years; FEV 1 , 108 ± 8% of predicted), using the Masterscreen PFT (Viasys/Jaeger; Hochberg, Germany), with 45 ppm of inspired nitric oxide (NO), and breath-hold times of 4 s, 6 s, 8 s, and 10 s. The last two of three consecutive measurements were used for analysis. Results In healthy subjects but not patients with CF, Dlno, and Dlco differed significantly (p Conclusions Single-breath determinations of dlno and dlco showed no difference between breath-hold times of 6 s and 8 s in subjects with or without airway obstruction, and reproducibility was acceptable. Standardization of breath-hold time for Dlno measurements seems important for clinical and research comparisons.

Objectives Histamine and cysteinyl leukotrienes play an important role in early (EAR) and late (LAR) allergen reactions. Although protection by anti-histamines and anti-leukotrienes has been studied extensively, little is known about the effect of their combination. We, therefore, assessed the effect of clinically recommended doses of azelastine and montelukast alone and in combination on EAR and LAR. Methods Seventeen patients (mean age 31 years, 14 m/3 f) with asthma and proven EAR and LAR received an oral dose of 4 mg azelastine twice daily, or 10 mg montelukast once daily, or both for 1 week, in a double-blind, double-dummy, cross-over fashion. FEV1 was measured after single-dose allergen challenges during EAR (0–2 h) and LAR (2–9 h). Results Azelastine, montelukast and their combination protected against both EAR and LAR ( p 0.004 , each) by 46% and 43%, 76% and 59%, and 89% and 78%, respectively. Azelastine was not as effective during EAR but equally effective to montelukast during LAR. The combination was superior to each drug alone during both EAR and LAR ( p 0.05 , each). Conclusion The combination of azelastine and montelukast in clinically recommended doses has a greater effect in suppressing early and late allergen reactions than each drug alone.

SummaryBackgroundPatients with severe COPD suffer from impairments of exercise capacity which affects daily activity. Conversely, activity might exert effects on the functional state. We studied whether a short-term intervention by regular phone calls caused an increase in activity at home and whether this resulted in a gain in exercise capacity.MethodsOver a 2-week period (P1) normal daily activity was assessed in 21 patients with stable severe COPD (GOLD III/IV). After this, the individual setting was explored in a short home visit. The subsequent 2-week period (P2) involved phone calls every other day to raise home-based activity (target: 3×15min daily at 75% of maximum dyspnea). During the study, patients wore an actograph plus pedometer and kept a diary. Before P1 and after P2, 6-min walking distance (6MWD), lung function, the Borg score and quality of life (SF-36, SGRQ) were determined.ResultsCompared to P1, actograph counts (p

SummaryBackgroundNatriuretic peptides are considered as reliable indicators of left-heart failure (HF) and are useful for differential diagnosis of dyspnoea.AimWe evaluated the clinical significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic hypercapnic respiratory failure (CHRF).MethodsIn 60 patients with CHRF, plasma concentrations of NT-proBNP were assessed at baseline and after treatment including non-invasive ventilation (NIV). The relationship of NT-proBNP to disease severity and its predictive value for survival were evaluated up to 4 years.ResultsNT-proBNP levels were markedly elevated in patients with CHRF (n=60; geometric mean (SD) 546.4 (4.9)pg/mL; p722pg/mL (67th percentile) and no adherence to NIV displayed poor prognosis (hazard ratio=0.21; 95%-CI=0.022–0.580; p=0.0091).ConclusionsNT-proBNP was highly elevated in patients with CHRF and correlated with the degree of respiratory impairment and exacerbation. Correspondingly, treatment including NIV led to reduction of NT-proBNP. These data indicate a potential role of NT-proBNP in assessing disease severity, treatment efficacy and prognosis in CHRF.

Patients with COPD and chronic hypercapnic respiratory failure (CHRF) are at high risk, and noninvasive ventilation at home is increasingly being used. Knowledge of prognostic parameters under these conditions is limited but may be clinically helpful and highlight the role of noninvasive ventilation.In 188 patients with COPD (mean +/- SD FEV1, 31.0 +/- 9.6% of predicted; PaCo2, 56.3 +/- 9.4 mm Hg) discharged from the hospital receiving NIV between July 1994 and July 2004, the prognostic value of body mass index (BMI), lung function, laboratory parameters, and blood gas levels was assessed by univariate and multivariate Cox regression analyses. Moreover, the impact of changes in risk factors on mortality assessed 6.7 +/- 2.8 months after the initiation of noninvasive ventilation was evaluated.Overall, the mortality rate during follow-up (duration, 32.2 +/- 24.3 months) was 44.7%, with 1-year, 2-year, and 5-year survival rates of 84.0%, 65.3%, and 26.4%. Deaths resulted predominantly from respiratory causes (73.8%). Univariate regression analyses revealed age, BMI, hemoglobin, FEV1, specific airway resistance, residual volume (RV)/total lung capacity (TLC), pH, and base excess (BE) to be associated with prognosis (p0.01 each), whereas multivariate analysis identified only age, BMI, RV/TLC, and BE as independent predictors (p0.05). In patients at risk (BMI25 km/m2, RV/TLCor= 73%, or BEor= 9 mmol/L), changes in these predictors were also associated with survival.In patients with COPD and CHRF, nutritional status, hyperinflation, and BE, which turned out to be reliable and consistent markers in CHRF, were independent prognostic factors for mortality. These data favor a multidimensional approach in these patients, including the use of noninvasive ventilation.

Budweiser S, Moertl M, Jorres RA, Windisch W, Heinemann F, Pfeifer M. Respiratory muscle training in restrictive thoracic disease: a randomized controlled trial. Objective To investigate the effects of respiratory muscle training (RMT) in patients with restrictive thoracic disorders and intermittent noninvasive positive-pressure ventilation (NPPV). Design Prospective randomized controlled trial. Setting Home-based RMT, with assessment in a primary care pulmonary center. Participants Thirty patients with restrictive thoracic disorders; 28 patients completed the trial. Intervention Three months of RMT by isocapnic hyperpnea or sham training. Main Outcome Measures Respiratory muscle strength and endurance, lung function, exercise performance, and health-related quality of life (HRQOL). Results After RMT, maximal inspiratory mouth pressure was increased (27.6%±36.5%, P =.013). In patients who could perform cycle ergometer testing (n=17), peak oxygen consumption (2.24±3.39mL·kg −1 ·min −1 vs −1.71±2.54mL·kg −1 ·min −1 , P =.014) and maximal work rate (9.4±14.8W vs −5.1±10.8W, P =.043) increased relative to a control group. Similar differences occurred regarding changes of HRQOL (physical performance, 3.3±11.4 score vs −6.6±9.0 score; P =.012) and time of ventilator use (−0.6±1.2h/d vs 0.4±0.5h/d, P =.010). Lung volumes, 12-second maximum voluntary ventilation, 6-minute walking distance, and blood gases were unchanged. Conclusions In patients with restrictive thoracic disorders and NPPV, RMT improved inspiratory muscle strength. Exercise performance and HRQOL were improved when the 2 groups were compared. RMT was practicable and safe despite severe respiratory impairment. Further evaluation, including different training intensities and modalities, seems warranted.

Hypertonic saline aerosol can elicit airway obstruction in patients with moderate or severe COPD. In the present study we assessed whether cetirizine dihydrochloride is capable of modulating this response. After a screening visit, 20 patients with COPD (mean FEV(1) 49% pred) were treated with cetirizine 10mg daily or placebo over 1 week in a randomized, double-blind, cross-over fashion and measurements performed at the end of treatment periods. At each visit, patients were challenged by 3% saline aerosol (screening: 0.9%) over 5 min after prior inhalation of salbutamol, and 45 min later sputum was obtained after inhalation of 0.9% saline. Lung function was quantified in terms of forced expiratory (FEV(1)) and inspiratory (FIV(1)) volumes. Spirometric values did not differ between visits and salbutamol-induced bronchodilation was not altered by cetirizine. Compared to baseline or post-salbutamol values, the saline-induced fall in FEV(1) was smallest at screening (P

Objective The effects of passive smoke exposure on respiratory health are still under debate. Therefore, we examined the risk of respiratory symptoms related to passive smoke exposure among German adults within the European Community Respiratory Health Survey. Methods The questionnaire data of the population-based sample (n = 1,890) were analyzed. Multiple logistic regression models were carried out for current asthma (asthma symptoms or medication), chronic bronchitis (cough with phlegm for ≥ 3 months per year), and wheezing as dependent variables, and self-reported exposure to passive smoke at home and at the workplace as independent variables after adjusting for city, age, gender, active smoking, and socioeconomic status as well as occupational exposure to dusts and/or gases. Results The relative odds for chronic bronchitis were significantly higher in subjects reporting involuntary tobacco smoke exposure in the workplace (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.16 to 3.11). Likewise, the adjusted OR for asthma was slightly elevated (OR, 1.51; 95% CI, 0.99 to 2.32). The risk of chronic bronchitis (OR, 3.07; 95% CI, 1.56 to 6.06), asthma (OR, 2.06; 95% CI, 1.07 to 3.97), and wheezing (OR, 2.12; 95% CI, 1.25 to 3.58) increased significantly with a daily exposure of > 8 h. Conclusion The control of passive smoke exposure in the workplace might reduce the risk of respiratory symptoms independently of exposure to other airborne contaminants.

Previous studies have shown higher prevalences of bronchial hyperresponsiveness (BHR), respiratory symptoms and atopic sensitization among adults in Western Germany than in Eastern Germany. One of the aims of the joint project INGA (INdoor Factors and Genetics in Asthma) is to assess incidence, prevalence and trends for asthma, BHR and atopic diseases over a time period of 11 years (1990–2001) in the former West (Hamburg) and East Germany (Erfurt), with special reference to indoor exposure.INGA was designed as a case-control study following a cross-sectional study performed from 1990 to 1992 within the European Community Respiratory Health Survey (ECRHS). The database consisted of 1159 subjects in Hamburg and 731 subjects in Erfurt from the ECRHS (age 20–44). In 1995–1996, 107 cases (diagnosed asthma, positive specific serum IgE, positive skin prick or PD20FEV1≤2·0 mg methacholine at ECRHS) and 106 controls (none of the previous findings) participated in Hamburg (115 cases and 109 controls in Erfurt). The methodology was identical to the ECRHS and dose–response slopes (DRS) of the methacholine challenge were calculated as an index of responsiveness.In the control group, median values of DRS were 0·028% mg−1(1990–1992) and 0·044 (1995–1996) (P

Background The purpose of this study was to develop a rapid and safe methacholine provocation protocol equivalent to the standard dosimeter technique. Methods The rapid protocol comprised a short and a long subprotocol. The challenge was started with one of these subprotocols according to the subject's answers to a questionnaire and baseline lung function. If FEV 1 dropped by 10% during the short subprotocol, the test was continued with the long subprotocol. The concentrations of methacholine and numbers of inhalations were chosen to match the concentrations of the standard method as closely as possible. To verify the protocol, we compared both methods in 38 subjects with asthma and 10 control subjects. Results The provocative concentrations of methacholine (PC 20 FEV 1 ) obtained with the standard method and the rapid method were within one doubling concentration in 38 of 40 subjects. None of the subjects who were normoreactive according to the standard method (PC 20 FEV 1 > 8 mg/mL) responded in the rapid protocol. The standard method required, on average (±SD), 34±11 min; the rapid method required 15 ±3 min. Conclusions The rapid provocation protocol is equivalent to the standard method, without loss in precision and safety, but with considerable saving in time. Therefore, it appears to be particularly suited for studies that require comparability with provocative concentrations obtained with the Rosenthal-Chai dosimeter method.

The aim of this study was to compare the susceptibility of peripheral monocytes and lymphocytes to oxidant-induced DNA single-strand breaks (SSB). DNA damage was assessed by the alkaline single-cell gel electrophoresis (SCGE) assay. Total peripheral mononuclear leukocytes (PML), PML enriched in lymphocytes and PML enriched in monocytes were used. The basal rate of SSB was measured after in vitro incubation of cells for 1 h in phosphate-buffered saline, and the induced rate after incubation in 10 microM or 50 microM H2O2. Incubation was performed at 4 degrees C to limit the possible influence of DNA repair. Lymphocyte-enriched PML were obtained after adhesion of the monocytes to tissue-culture treated plastic, and monocyte-enriched PML by removal of monocytes from the plastic through trypsin. In all samples, cell differentiation was performed using an immunofluorescence technique with antibodies against T- and B-lymphocytes and cytospin preparations. The rate of SSB was determined by visual scoring according to 6 predefined categories of DNA damage and was expressed as mean score (range 0-500) per 100 cells. There was a linear relationship between the percentage of lymphocytes in the samples and the basal rate of SSB (p0.001, slope 0.67 score units per %). The same was true for induced DNA damage after incubation in 10 microM H2O2 (p0.001, slope 3.80 score units per %) or 50 microM H2O2 (p0.001, slope 3.22 score units per %). These regression analyses revealed a 2.9-fold greater rate of basal DNA damage in lymphocytes compared to monocytes and an 11.3-fold greater rate for the damage induced by 10 microM H2O2. We conclude that there are marked differences in the rate of basal and induced SSB between lymphocytes and monocytes, suggesting differences in antioxidant capacity between the two cell populations. These findings indicate that the assessment of SSB for biomonitoring and genotoxicity testing using PML has to take into account possible changes in cellular composition.

We describe five patients with severe nocturnal cough and daytime somnolence in whom the coughing attacks are triggered by assuming the supine body position. Quantity and quality of the nocturnal cough were evaluated in the sleep laboratory with and without nasal continuous positive airway pressure (N-CPAP). Air flow characteristics were assessed using flow volume and airway resistance loops. Airway anatomy was evaluated bronchoscopically. In all five patients, the cough had a barking quality. Flow-volume loops showed an expiratory collapse phenomenon in two of the patients. Endoscopically, all five patients had signs of airway collapse. All patients had difficulty falling asleep because of coughing and were awakened by it frequently. Sleep times ranged from 2.5 to 4.5 h per night. With N-CPAP pressures ranging from 5 to 13 cm H 2 O, all five patients had clinically significant improvement in their symptoms. Their sleep times increased to a range of 5 to 7.5 h per night and the daytime somnolence markedly improved or resolved. All five patients requested a N-CPAP unit for home use. We conclude that a cough that is predominantly associated with or exacerbated by the supine body position may be treated effectively with N-CPAP. (CHEST 1995; 108:581-85)

To compare the acute bronchodilator effect of increasing doses of intravenous theophylline and inhaled beta adrenergic agonists, we administered intravenous theophylline dissolved in ethylenediamine or proxyphylline and diprophylline or placebo in a double blind fashion to nine asthmatics on three different days. At each session, 100 mg theophylline or placebo were given during each of five subsequent periods of 30 minutes' duration and followed by inhalation of 0.4 mg fenoterol. In contrast to placebo, 500 mg theophylline in ethylenediamine or proxyphylline and diprophylline significantly decreased mean specific airway resistance (SRaw in cmH 2 O•s) from 31.2 to 23.6 or 34.2 to 23.5 at theophylline serum concentrations of 14.4 or 16.6 mg/L, respectively. Fenoterol lowered SRaw to about 40 percent of the respective baseline values independent of theophylline or placebo pretreatment. We conclude that the acute bronchodilator effect of theophylline is weak in comparison to inhaled beta agonists. Furthermore, proxyphylline and diprophylline cause a weak but not significant bronchodilation when compared to ethylenediamine.